Molecular epidemiology and mechanisms of tigecycline resistance in carbapenem-resistantKlebsiella pneumoniaeisolates

Background The emergence and transmission of tigecycline- and carbapenem-resistantKlebsiella pneumoniae(TCRKP) have become a major concern to public health globally. Here, we investigated the molecular epidemiology and mechanisms of tigecycline resistance in carbapenem-resistantK pneumoniae(CRKP) isolates. Methods Forty-five non-duplicate CRKP isolates were collected from January 2017 to June 2019. We performed antimicrobial susceptibility tests, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). PCR and DNA sequencing were performed for the detection and mutation analysis ofacrR,oqxR,ramR,rpsJ,tet(A), andtet(X)genes, which are related to tigecycline resistance. The expression levels of efflux pump genesacrBandoqxBand their regulator genesrarA,ramA,soxS, andmarAwere assessed by quantitative real-time PCR. Results The resistance rate to tigecycline in CRKP isolates was 37.8% (17/45).K pneumoniaeST307 was a predominant clone type (70.6%, 12/17) among the TCRKP isolates. The expression levels ofacrB(P < .001) andmarA(P = .009) were significantly higher in the tigecycline-resistant group than in the tigecycline-intermediate and tigecycline-susceptible groups. Increased expression ofacrBwas associated withmarAexpression (r = 0.59,P = .013). Conclusions We found that the activated MarA-induced overexpression of AcrAB efflux pump plays an important role in the emergence of tigecycline resistance in CRKP isolates.